Uri Dinnar

A membrane micropump electrostatically actuated across the working fluid

A novel electrostatically actuated valveless micropump is presented whereby an actuation voltage is applied across a working fluid, which takes advantage of the higher relative electrical permittivity of water and many other fluids with respect to air. The device is fabricated in silicon and the diaphragm is made of electroplated nickel, while the assembly is carried out using flip–chip bonding. A reduced-order model is used to describe the micropumps performance in terms of electrical properties of the fluid, the residual stress in the diaphragm, geometrical features and the actuation voltage. The tested prototype featured a ~1 µl min−1 flow rate at 50 V actuation voltage. The model predictions show the possibility of achieving flow rates >1 µl min−1 with the actuation voltage <10 V for devices with 3 mm diaphragm size.

A parametric study of human fibroblasts culture in a microchannel bioreactor

The culture of cells in a microbioreactor can be highly beneficial for cell biology studies and tissue engineering applications. The present work provides new insights into the relationship between cell growth, cell morphology, perfusion rate, and design parameters in microchannel bioreactors. We demonstrate the long-term culture of mammalian (human foreskin fibroblasts, HFF) cells in a microbioreactor under constant perfusion in a straightforward simple manner. A perfusion system was used to culture human cells for more than two weeks in a plain microchannel (130 microm x 1 mm x 2 cm). At static conditions and at high flow rates (>0.3 ml h(-1)), the cells did not grow in the microchannel for more than a few days. For low flow rates (<0.2 ml h(-1)), the cells grew well and a confluent layer was obtained. We show that the culture of cells in microchannels under perfusion, even at low rates, affects cell growth kinetics as well as cell morphology. The oxygen level in the microchannel was evaluated using a mass transport model and the maximum cell density measured in the microchannel at steady state. The maximum shear stress, which corresponds to the maximum flow rate used for long term culture, was 20 mPa, which is significantly lower than the shear stress cells may endure under physiological conditions. The effect of channel size and cell type on long term cell culture were also examined and were found to be significant. The presented results demonstrate the importance of understanding the relationship between design parameters and cell behavior in microscale culture system, which vary from physiological and traditional culture conditions.

Design of well and groove microchannel bioreactors for cell culture.

Microfluidic bioreactors have been shown valuable for various cellular applications. The use of micro‐wells/grooves bioreactors, in which micro‐topographical features are used to protect sensitive cells from the detrimental effects of fluidic shear stress, is a promising approach to culture sensitive cells in these perfusion microsystems. However, such devices exhibit substantially different fluid dynamics and mass transport characteristics compared to conventional planar microchannel reactors. In order to properly design and optimize these systems, fluid and mass transport issues playing a key role in microscale bioreactors should be adequately addressed. The present work is a parametric study of micro‐groove/micro‐well microchannel bioreactors. Operation conditions and design parameters were theoretically examined via a numerical model. The complex flow pattern obtained at grooves of various depths was studied and the shear protection factor compared to planar microchannels was evaluated. 3D flow simulations were preformed in order to examine the shear protection factor in micro‐wells, which were found to have similar attributes as the grooves. The oxygen mass transport problem, which is coupled to the fluid mechanics problem, was solved for various groove geometries and for several cell types, assuming a defined shear stress limitation. It is shown that by optimizing the groove depth, the groove bioreactor may be used to effectively maximize the number of cells cultured within it or to minimize the oxygen gradient existing in such devices. Moreover, for sensitive cells having a high oxygen demand (e.g., hepatocytes) or low endurance to shear (e.g., human embryonic stem cells), results show that the use of grooves is an enabling technology, since under the same physical conditions the cells cannot be cultured for long periods of time in a planar microchannel. In addition to the theoretical model findings, the culture of human foreskin fibroblasts in groove (30 µm depth) and well bioreactors (35 µm depth) was experimentally examined at various flow rates of medium perfusion and compared to cell culture in regular flat microchannels. It was shown that the wells and the grooves enable a one order of magnitude increase in the maximum perfusion rate compared to planar microchannels. Altogether, the study demonstrates that the proper design and use of microgroove/well bioreactors may be highly beneficial for cell culture assays. Biotechnol. Bioeng. 2009;102: 1222–1230.

Ion-sensitive field-effect transistors in standard CMOS fabricated by post processing

Highly integrated ion-sensitive field-effect transistor (ISFET) microsystems require the monolithic implementation of ISFETs, CMOS electronics, and additional sensors on the same chip. This paper presents new ISFETs in standard CMOS, fabricated by post-processing of a standard CMOS VLSI chip. Unlike CMOS compatible ISFETs fabricated in a dedicated process, the new sensors are directly combined with state-of-the-art CMOS electronics and are subject to continuous technology upgrading. The ISFETs presented include an intermediate gate formed by one or more conducting layers placed between the gate oxide and the sensing layer. The combination of the highly isolating gate oxide of the MOS with a leaky or conducting sensing layer allows the use of low temperature materials that do not damage the CMOS chip. The operation of ISFETs with an intermediate gate and sensing layers fabricated at low temperature is modeled. ISFETs with a linear pH response and drift as low as 0.3 mV/h are reported.

An Analytical Descrptor of Three-Dimensional Geometry: Application to the Analysis of the Left Ventricle Shape and Contraction

A novel method to describe the instantaneous three-dimensional (3-D) geometry of the left ventricular (LV) endocardial surface by an analytical time-varying scalar function of Fourier spectrum coefficients is suggested. The method utilizes experimental echocardiographic data and uses a helical coordinate system to transform the 3-D data into a unidimensional numerical function. The instantaneous numerical function is then represented by its Fourier sine series which serves as an analytical shape descriptor from which the 3-D shape is reconstructed. The procedure can also be applied to data compression (spatial low-pass filtering), spectral analysis, and the evaluation of geometric similarity of 3-D shapes. When applied to the endocardial surface of the LV at end-diastole (ED) and end-systole (ES) this technique gives a quantitative analysis of the global LV contraction of the real heart.

Computer studies of systemic and regional blood flow mechanisms during cardiopulmonary resuscitation

Based on the new concept that intrathoracic and abdominal pressure variations cause blood flow in most of the cardiopulmonary resuscitation (CPR) techniques, two mathematical models were developed to explore related mechanisms of blood flow. The models were based on a representation of the cardiovascular system by resistive, capacitive and inductive elements, and the existence of venous and cardiac unidirectional valves. Cyclic intrathoracic and abdominal pressure variations were simulated by modulating the pressure within the corresponding vessels. It was found that blood flow during CPR is highly dependent on venous valving and aortic valve competence. The systemic blood flow was calculated to be between 10 and 20 per cent of its normal value. The maximum flow under a cyclic pressure of 50 mmHg was 663 m/min−1, which was achieved with a pulse rate of 115 cycles per min and a duty cycle (ratio of artificial systole to cycle duration) of 58 per cent. The coronary blood flow was found to occur only during artificial diastole and was actually reversed during the compression phase. The systemic blood flow increased when pressure variations were delivered to the chest alone or when some phase lag was introduced between the thoracic and abdominal pressure waves. The mathematical model presented provided a tool to study the effect of thoracic and abdominal pressure waves on the circulation in CPR. The information derived from the model can be used to design better methods for CPR.

A note on the theory of deformation in compressed skin tissues

Abstract An analytical model for tissue behavior under pressure in proposed. The model consists of an arrangement of springs and dashpots. Such models are, of course, well known, but do not appear to have been proposed previously for skin tissue. The model relates the viscoelastic properties of the skin tissue to quantities that can be measured in vivo , such as instantaneous elastic compression, delayed elastic recovery, and molding deformation. So if some in vivo measurements can be carried out to measure these quantities, this model can be used to determine the viscoelastic properties of skin tissue. The model is checked for normal conditions, as well as conditions of lymphatic disease or disability, and compared with clinical measurements.

Analysis of flow in coronary epicardial arterial tree and intramyocardial circulation

A mathematical model combining the coronary flow in the epicardial arterial tree and the intramyocardial circulation is presented. The epicardial arterial tree is represented by a resistive capacitive network based on its realistic anatomy. The intramyocardial flow is affected by the pump action of the contracting myocardium through the extravascular compressive pressure (ECP), which, in turn, affects the dynamic resistance and compliance changes based on the relationship between the transmular pressure and the cross-sectional area of a vessel. The model accounts for the autoregulatory mechanism of the intramyocardial compartments (arteriolar, microvascular and venular) and is structured according to the epicardial coronary anatomy. Realistic coronary epicardial arterial flow patterns are obtained, which compare well to experimentally measured data in six dogs under basal conditions and during reactive hyperemic response. Simulations of the average transmural flow in the three intramyocardial vascular compartments show that the flow in the arterial side is predominantly diastolic, with a systolic retrograde component, and is dominantly systolic antegrade flow in the venular side, consistent with experimental data. Interestingly, the transmurally average microcirculatory flow is continuous, with very small change throughout the cardiac cycle, and is practically insensitive to changes in the model parameters. The model presents a quantitative tool that describes the dynamic pattern of coronary flow in relationship to muscular and extravascular parameters.

ISFET CMOS compatible design and encapsulation challenges

This work presents the main challenges in ISFET encapsulation. It analyzes SU8 drawbacks as an encapsulant and presents a novel flip-chip bonding packaging concept.

Effect of vest cardiopulmonary resuscitation rate on cardiac output and coronary blood flow.

We studied the effect of CPR rate on the hemodynamic indices of surgically instrumented canine experimental models. Using pneumatic vest CPR, we applied simultaneous rib cage and abdominal compressions at rates of 1 to 12 Hz. CPR with 2-Hz frequency yielded the highest aortic and coronary flows (252 +/- 14 and 6.8 +/- 1.1 ml/min vs. 178 + 12 and 0.96 +/- 0.08 ml/min at 1 Hz, respectively; p less than .005). The validity of the present American Heart Association recommendation for 1-Hz CPR rate would benefit from further studies.